Figure 3.

Berzosertib inhibits SARS-CoV-2, SARS-CoV-1, and MERS-CoV replication in human cells and is synergistic with remdesivir

(A and B) Graphs show an eight-point dose-response curve of berzosertib (A) or remdesivir (B) in SARS-CoV-2-infected Calu-3 cells. Contrasted with cell viability of mock-infected cells.

(C and D) Antiviral effect of berzosertib on SARS-CoV-1 (C) and MERS-CoV (D).

(E) Graphs show antiviral activity measured with a SARS-CoV-2 immunostaining signal used for identification of infected A549-ACE2 cells. IC₅₀ values were calculated by non-linear regression sigmoidal dose-response analysis using the GraphPad Prism 7 software package.

(F) Graph shows synergistic effect of berzosertib and remdesivir in infected A549-ACE2 cells. Dose-response curves obtained with mixtures of remdesivir and berzosertib, remdesivir alone (thick black line), and berzosertib alone (thick pink line) are shown.

(G) Isobologram of drug combinations is depicted.

(H) Combinatorial data were analyzed for inhibitory, additive, or synergistic effects (upper triangle, dotted line, and lower triangle, respectively) by using the Compusyn software package.